This is the first of three chapters on biologic heterocycles as central chemical and metabolic building blocks. This chapter focuses specifically on the pyrimidine and purine building blocks for RNA and DNA. The four functional groups of amides, amidines, ureas, and guanidines dictate the hydrogen bonding rules for Watson–Crick base pairing in double helical DNA. The biosynthetic logic for both the monocyclic pyrimidine nucleotides, uridine monophosphate and cytidine triphosphate, and the bicyclic purines, adenosine monophosphate, and guanosine monophosphate, are evaluated based on simple metabolic building blocks and likely ancient chemical logic.